tbuckley/cabot-search huggingface dataset:
Referring and Specialist Physician Gender and Specialist Billing
Authors: Nadine Chami, Sharada Weir, Shaun A. Shaikh, Lyn M. Sibley, Sarah Simkin, James G. Wright, Jasmin Kantarevic
Journal: JAMA Network Open (2023)

While a gender pay gap in medicine has been well documented, relatively little research has addressed mechanisms that mediate gender differences in referral income for specialists.To examine gender-based disparities in medical and surgical specialist referrals in Ontario, Canada.This cross-sectional study included referrals for specialist care ascertained from Ontario Health Insurance Plan physician billings for fiscal year 2018 to 2019. Participants were specialist physicians who received new patient consultations from April 1, 2018, to March 31, 2019, and the associated referring physicians. Data were analyzed from April 2018 to March 2020, including a 12-month follow-up period.Specialist and referring physician gender (female or male).Revenue per referral was defined based on an episode-of-care approach as total billings for a 12-month period from the initial consultation. Mean total billings for female and male specialists were compared and the differential divided into the portion owing to referral volume vs referral revenue. Difference-in-differences multivariable regression analysis was used to estimate gender-based differences in revenue per referral. For each referring physician, gender-based differences in referral patterns were examined using case-control analysis, in which specialists who received a referral were compared with matched control specialists who did not receive a referral. This analysis considered the gender of the specialist and concordance between the gender of the referring physician and specialist, among other characteristics.Of 7 621 365 new referrals, 32 824 referring physicians, of whom 13 512 (41.2%) were female (mean [SD] age, 46.3 [11.6] years) and 19 312 (58.8%) were male (mean [SD] age, 52.9 [13.5] years), made referrals to 13 582 specialists, of whom 4890 (36.0%) were female (mean [SD] age, 45.6 [11.0] years) and 8692 (64.0%) were male (mean [SD] age, 51.8 [13.0] years). Male specialists received more mean (SD) referrals than did female specialists (633 [666] vs 433 [515]), and the mean (SD) revenue per referral was higher for males ($350 [$474]) compared with females ($316 [$393]). Adjusted analysis demonstrated a -4.7% (95% CI, -4.9% to -4.5%) difference in the revenue per referral between male and female specialists. Multivariable regression analysis found that physicians referred more often to specialists of the same gender (odds ratio, 1.04; 95% CI, 1.03-1.04) but had higher odds of referring to male specialists (odds ratio, 1.10; 95% CI, 1.09-1.11).In this cross-sectional study of the gender pay gap in specialist referral income, the number and revenue from referrals received differed by gender, as did the odds of receiving a referral from a physician of the same gender. Future research should examine the effectiveness of different policies to address this gap, such as a centralized, gender-blinded referral system.
FDA Approval Summary: Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma
Authors: Deepti Telaraja, Yvette L. Kasamon, Justin S. Collazo, Ruby Leong, Kun Wang, Ping Li, Elyes Dahmane, Yuching Yang, Justin Earp, Manuela Grimstein, Lisa R. Rodriguez, Marc R. Theoret, Nicole J. Gormley
Journal: Clinical Cancer Research (2023)

Abstract In January 2023, the FDA granted accelerated approval to pirtobrutinib for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor. Approval was based on BRUIN, a single-arm study of pirtobrutinib monotherapy in patients with B-cell malignancies. Efficacy was based on independent review committee–assessed overall response rate (ORR) supported by durability of response in 120 patients with relapsed or refractory MCL who had received a prior BTK inhibitor and received the approved pirtobrutinib dosage of 200 mg once daily. The ORR was 50% [95% confidence interval (CI), 41–59], and the complete response rate was 13% (95% CI, 7–20), with an estimated median duration of response of 8.3 months. The most common nonhematologic adverse reactions were fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising. Warnings and Precautions in labeling include infection, hemorrhage, cytopenias, atrial arrhythmias, and second primary malignancies. Postmarketing studies were required to evaluate longer-term safety of pirtobrutinib and to verify the clinical benefit of pirtobrutinib. This article summarizes key aspects of the regulatory review, including the indication statement, efficacy and safety considerations, and postmarketing requirements.
Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity
Authors: Mikhail N Kosiborod, Steen Z Abildstrøm, Barry A Borlaug, Javed Butler, Søren Rasmussen, Melanie Davies, G Kees Hovingh, Dalane W Kitzman, Marie L Lindegaard, Daniél V Møller, Sanjiv J Shah, Marianne B Treppendahl, Subodh Verma, Walter Abhayaratna, Fozia Z Ahmed, Vijay Chopra, Justin Ezekowitz, Michael Fu, Hiroshi Ito, Małgorzata Lelonek, Vojtech Melenovsky, Bela Merkely, Julio Núñez, Eduardo Perna, Morten Schou, Michele Senni, Kavita Sharma, Peter Van der Meer, Dirk von Lewinski, Dennis Wolf, Mark C Petrie
Journal: New England Journal of Medicine (2023)

BackgroundHeart failure with preserved ejection fraction is increasing in prevalence and is associated with a high symptom burden and functional impairment, especially in persons with obesity. No therapies have been approved to target obesity-related heart failure with preserved ejection fraction.MethodsWe randomly assigned 529 patients who had heart failure with preserved ejection fraction and a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or higher to receive once-weekly semaglutide (2.4 mg) or placebo for 52 weeks. The dual primary end points were the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating fewer symptoms and physical limitations) and the change in body weight. Confirmatory secondary end points included the change in the 6-minute walk distance; a hierarchical composite end point that included death, heart failure events, and differences in the change in the KCCQ-CSS and 6-minute walk distance; and the change in the C-reactive protein (CRP) level.Download a PDF of the Research Summary.ResultsThe mean change in the KCCQ-CSS was 16.6 points with semaglutide and 8.7 points with placebo (estimated difference, 7.8 points; 95% confidence interval [CI], 4.8 to 10.9; P<0.001), and the mean percentage change in body weight was −13.3% with semaglutide and −2.6% with placebo (estimated difference, −10.7 percentage points; 95% CI, −11.9 to −9.4; P<0.001). The mean change in the 6-minute walk distance was 21.5 m with semaglutide and 1.2 m with placebo (estimated difference, 20.3 m; 95% CI, 8.6 to 32.1; P<0.001). In the analysis of the hierarchical composite end point, semaglutide produced more wins than placebo (win ratio, 1.72; 95% CI, 1.37 to 2.15; P<0.001). The mean percentage change in the CRP level was –43.5% with semaglutide and –7.3% with placebo (estimated treatment ratio, 0.61; 95% CI, 0.51 to 0.72; P<0.001). Serious adverse events were reported in 35 participants (13.3%) in the semaglutide group and 71 (26.7%) in the placebo group.ConclusionsIn patients with heart failure with preserved ejection fraction and obesity, treatment with semaglutide (2.4 mg) led to larger reductions in symptoms and physical limitations, greater improvements in exercise function, and greater weight loss than placebo. (Funded by Novo Nordisk; STEP-HFpEF ClinicalTrials.gov number, NCT04788511.) Quick Take Semaglutide in Heart Failure with Obesity 2m 5s
Targeting cholesterol homeostasis through inhibiting SREBP-2: An Achilles’ heel for glioblastoma
Authors: Yanfei Sun, Guangjing Mu, Zhiwei Xue, Shuai Wang, Xingang Li, Mingzhi Han
Journal: Neuro-Oncology (2023)

Targeting cholesterol homeostasis through inhibiting SREBP-2: An Achilles' heel for glioblastomaWe read with great interest the recent study by Gu et al. 1 entitled SREBP-2 maintains glioblastoma stem cells through keeping the balance between cholesterol biosynthesis and uptake.Sterol regulatory element-binding proteins (SREBPs) are crucial lipogenesis-regulating transcription factors that include SREBP-1 (SREBP-1a, SREBP-1c) and SREBP-2.SREBP-1 mainly stimulates fatty acid synthesis, while SREBP-2 targets mostly genes involved in cellular cholesterol homeostasis.Targeting this family provides new insights into treatment of neoplasms.The authors performed a study aiming at investigating the crucial role of SREBP-2 in cholesterol homeostasis in glioblastoma stem cells (GSCs) as well as self-renewal and tumorigenesis. 1 As blocking cholesterol metabolism has been recognized as a potential disincentive for malignant performance of glioblastoma (GBM), the detailed mechanism confirmed and novel targets revealed by this research work encourage exploration of new therapeutic strategies.However, several aspects of the study deserve attention.First, the authors used Betulin as an inhibitor of SREBP-2 to attenuate GSC growth.However, Betulin showed low specificity and could function as an inhibitor for both SREBP-1 and SREBP-2. 2 Based on a previous study, 3 SREBP-1 was proven to contribute to GBM progression and tumorigenesis, and it owned higher expression level and prognostic relevance than SREBP-2.Thus, the authors did not assess effects of selective SREBP-2 blockade, and the observed effects could be influenced by inhibition of SREBP-1.In addition, it was reported that Betulin could not cross blood-brain barrier, limiting its clinical translation potential. 4Recently, novel inhibitors (PCSK9-IN-9 and 5-O-methylembelin) have been reported to
Efficacy of Different Powers of Low-Level Red Light in Children for Myopia Control
Authors: Wen Zhou, Ya Liao, Wei Wang, Yanmei Sun, Qin Li, Siqi Liu, Jie Tang, Lin Li, Xiaojuan Wang
Journal: Ophthalmology (2023)

To compare the efficacy and safety of low-level red light (LRL) in controlling myopia progression at 3 different powers: 0.37 mW, 0.60 mW, and 1.20 mW.Single-center, single-masked, randomized controlled trial.Two hundred children aged 6-15 with myopia of -0.50 diopter (D) or more and astigmatism of -2.50 D or less were enrolled from April to May 2022. Follow-up ended in December 2022.Participants were assigned randomly to 3 intervention groups and 1 control group (1:1:1:1). All participants wore single-vision spectacles. Moreover, the intervention group randomly received LRL at 3 different powers twice daily for 3 minutes per session, with a minimum 4-hour interval.Changes in spherical equivalent (SE), axial length (AL), and subfoveal choroidal thickness (SFCT) were measured.After 6 months, SE progression was significantly lower in the 0.37-mW group (0.01 D; 95% confidence interval [CI], -0.12 to 0.15), 0.60-mW group (-0.05 D; 95% CI, -0.18 to 0.07), and 1.20-mW group (0.16 D; 95% CI, 0.03 to 0.30) compared to the control group (-0.22 D; 95% CI, -0.50 to 0.30; adjusted P < 0.001 for all). AL changes in the 0.37-mW group (0.04 mm; 95% CI, -0.01 to 0.08), 0.60-mW group (0.00 mm; 95% CI, -0.05 to 0.05), and 1.20-mW group (-0.04 mm; 95% CI, -0.08 to 0.01) were significantly smaller than the control group (0.27 mm; 95% CI, 0.22 to 0.33; adjusted P < 0.001 for all). Similarly, increases in SFCT were significantly greater in the 0.37-mW group (22.63 μm; 95% CI, 12.13 to 33.34 μm), 0.60-mW group (36.17 μm; 95% CI, 24.37 to 48.25 μm), and 1.20-mW group (42.59 μm; 95% CI, 23.43 to 66.24 μm) than the control group (-5.07 μm; 95% CI, -10.32 to -0.13 μm; adjusted P < 0.001 for all). No adverse events were observed.LRL effectively controlled myopia progression at 0.37 mW, 0.60 mW, and 1.20 mW. Further research is required.The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Genetic inactivation of β-catenin is salubrious, whereas its activation is deleterious in desmoplakin cardiomyopathy
Authors: Melis Olcum, Siyang Fan, Leila Rouhi, Sirisha Cheedipudi, Benjamin Cathcart, Hyun-Hwan Jeong, Zhongming Zhao, Priyatansh Gurha, Ali J Marian
Journal: Cardiovascular Research (2023)

Mutations in the DSP gene encoding desmoplakin, a constituent of the desmosomes at the intercalated discs (IDs), cause a phenotype that spans arrhythmogenic cardiomyopathy (ACM) and dilated cardiomyopathy. It is typically characterized by biventricular enlargement and dysfunction, myocardial fibrosis, cell death, and arrhythmias. The canonical wingless-related integration (cWNT)/β-catenin pathway is implicated in the pathogenesis of ACM. The β-catenin is an indispensable co-transcriptional regulator of the cWNT pathway and a member of the IDs. We genetically inactivated or activated β-catenin to determine its role in the pathogenesis of desmoplakin cardiomyopathy.
Failure of scabies treatment: a systematic review and meta-analysis
Authors: Lawrence Mbuagbaw, Behnam Sadeghirad, Rebecca L Morgan, Dominik Mertz, Shahrzad Motaghi, Maryam Ghadimi, Ifeoluwa Babatunde, Babalwa Zani, Tejanth Pasumarthi, McKenzie Derby, Venkata N Kothapudi, Nicole R Palmer, Anton Aebischer, Thomas Harder, Felix Reichert
Journal: British Journal of Dermatology (2023)

Abstract Background Treatment failure is considered to be an important factor in relation to the increase in scabies incidence over the last decade. However, the regional and temporal differences, in addition to the predictors of therapy failure, are unclear. Objectives We aimed to conduct a systematic review of the prevalence of treatment failure in patients with scabies and investigation of associated factors. Methods We searched MEDLINE, EMBASE, CINAHL, Web of Science, Scopus, Global Health and the Cochrane Central Register of Controlled Trials from inception to August 2021 for randomized and quasi-randomized trials, in addition to observational studies that enrolled children or adults diagnosed with confirmed or clinical scabies treated with permethrin, ivermectin, crotamiton, benzyl benzoate, malathion, sulfur or lindane, and measured treatment failure or factors associated with treatment failure. We performed a random effects meta-analysis for all outcomes reported by at least two studies. Results A total of 147 studies were eligible for inclusion in the systematic review. The overall prevalence of treatment failure was 15.2% [95% confidence interval (CI) 12.9–17.6; I2 = 95.3%, moderate-certainty evidence] with regional differences between World Health Organization regions (P = 0.003) being highest in the Western Pacific region (26.9%, 95% CI 14.5–41.2). Oral ivermectin (11.8%, 95% CI 8.4–15.4), topical ivermectin (9.3%, 95% CI 5.1–14.3) and permethrin (10.8%, 95% CI 7.5–14.5) had relatively lower failure prevalence compared with the overall prevalence. Failure prevalence was lower in patients treated with two doses of oral ivermectin (7.1%, 95% CI 3.1–12.3) compared with those treated with one dose (15.2%, 95% CI 10.8–20.2; P = 0.021). Overall and permethrin treatment failure prevalence in the included studies (1983–2021) increased by 0.27% and 0.58% per year, respectively. Only three studies conducted a multivariable risk factor analysis; no studies assessed resistance. Conclusions A second dose of ivermectin showed lower failure prevalence than single-dose ivermectin, which should be considered in all guidelines. The increase in treatment failure over time hints at decreasing mite susceptibility for several drugs, but reasons for failure are rarely assessed. Ideally, scabicide susceptibility testing should be implemented in future studies.
The neglect of kwashiorkor
Authors: Thaddaeus May, Esther Babirekere-Iriso, Mamady Traoré, Emmanuel Berbain, Maimuna Ahmed, Beatrice Amadi, André Briend, Mark Manary, Aminata Shamit Koroma, Neil Hanchard, Mette Frahm Olsen, Henrik Friis, George PrayGod, Tsinuel Girma, Moustapha Moussa, Aboubacar Mahamadou, Peter Hotez, Haoua Seini Sabo
Journal: The Lancet Child & Adolescent Health (2023)
Value of intravenous thrombolysis in endovascular treatment for large-vessel anterior circulation stroke: individual participant data meta-analysis of six randomised trials
Authors: Charles B Majoie, Fabiano Cavalcante, Jan Gralla, Pengfei Yang, Johannes Kaesmacher, Kilian M Treurniet, Manon Kappelhof, Bernard Yan, Kentaro Suzuki, Yongwei Zhang, Fengli Li, Masafumi Morimoto, Lei Zhang, Zhongrong Miao, Leon A Rinkel, Jiacheng Huang, Toshiaki Otsuka, Shouchun Wang, Stephen Davis, Christophe Cognard, Bo Hong, Jonathan M Coutinho, Jiaxing Song, Wenhuo Chen, Bart J Emmer, Omer Eker, Liyong Zhang, Tomas Dobrocky, Huy-Thang Nguyen, Steven Bush, Ya Peng, Natalie E LeCouffe, Masataka Takeuchi, Hongxing Han, Yuji Matsumaru, Daniel Strbian, Hester F Lingsma, Daan Nieboer, Qingwu Yang, Thomas Meinel, Peter Mitchell, Kazumi Kimura, Wenjie Zi, Raul G Nogueira, Jianmin Liu, Yvo B Roos, Urs Fischer, Wenjie Zi, Raul Nogueira, Qingwu Yang, Jianmin Liu, Pengfei Yang, Yongwei Zhang, Bernard Yan, Peter Mitchell, Zhong Rong Miao, Charles B. Majoie, Yvo B. Roos, Kentaro Suzuki, Kazumi Kimura, Yuji Matsumaru, Urs Fischer, Jan Gralla, Fabiano W. Cavalcante, Manon Kappelhof, Kilian M. Treurniet, Johannes Kaesmacher, Lei Zhang, Steven Bush, Daan Nieboer, Hester F. Lingsma, Peter Rothwell, Jeffrey Saver, Jens Fiehler, Fengli Li, Jiacheng Huang, Jiaxing Song, Bo Hong, Wenhuo Chen, Ya Peng, Hongxing Han, Liyong Zhang, Zifu Li, Pengfei Xing, Hongjian Shen, Ping Zhang, Xiaoxi Zhang, Stephen Davis, Huy-Thang Nguyen, Geoffrey Donnan, Xiaochuan Huo, Guangxian Nan, Andrew Bivard, Henry Ma, Dang Lu Vu, Bruce Campbell, Leon A. Rinkel, Bart J. Emmer, Jonathan M. Coutinho, Natalie E. LeCouffe, Diederik W. Dippel, Aad van der Lugt, Wim H. van Zwam, Robert J. van Oostenbrugge, Maarten Uyttenboogaart, Vincent Costalat, Geert Lycklama, Jeannette Hofmeijer, Anouk van Norden, Toshiaki Otsuka, Masataka Takeuchi, Masafumi Morimoto, Ryuzaburo Kanazawa, Yohei Takayama, Yuki Kamiya, Keigo Shigeta, Seiji Okubo, Mikito Hayakawa, Daniel Strbian, Omer Eker, Christophe Cognard, Thomas Meinel, Tomas Dobrocky, Simon Jung, Eike Piechowiak, Gaultier Marnat, Igor Sibon, Romain Bourcier, Solene de Gaalon, Chrysanthi Papagiannaki, Margaux Lefebvre
Journal: The Lancet (2023)
Do doctors need to be told to be kind?
Authors: Daniel Sokol
Journal: BMJ (2023)

the General Medical Council (GMC) published the latest version of Good Medical Practice, its guidance for doctors. 1 The guidance will come into effect on 30 January 2024, but it has already been widely debated by doctors on social media.The target of the discussion is the introduction of a requirement to treat patients and colleagues with "kindness, courtesy, and respect."Critics of the guidance say "kindness" is too subjective.They say it is patronising.They say it will prevent doctors from speaking out, or sharing unpleasant news.They say it will result in frivolous complaints and referrals to the GMC, with a disproportionate impact on women and doctors trained abroad.
SCA: recovering single-cell heterogeneity through information-based dimensionality reduction
Authors: Benjamin DeMeo, Bonnie Berger
Journal: Genome biology (2023)

Abstract Dimensionality reduction summarizes the complex transcriptomic landscape of single-cell datasets for downstream analyses. Current approaches favor large cellular populations defined by many genes, at the expense of smaller and more subtly defined populations. Here, we present surprisal component analysis (SCA), a technique that newly leverages the information-theoretic notion of surprisal for dimensionality reduction to promote more meaningful signal extraction. For example, SCA uncovers clinically important cytotoxic T-cell subpopulations that are indistinguishable using existing pipelines. We also demonstrate that SCA substantially improves downstream imputation. SCA’s efficient information-theoretic paradigm has broad applications to the study of complex biological tissues in health and disease.
Medications for alcohol use disorder promote abstinence in alcohol-associated cirrhosis: Results from a systematic review and meta-analysis
Authors: Jordi Gratacós-Ginès, Pol Bruguera, Martina Pérez-Guasch, Ana López-Lazcano, Roger Borràs, Helena Hernández-Évole, Maria T. Pons-Cabrera, Anna Lligoña, Ramón Bataller, Pere Ginès, Hugo López-Pelayo, Elisa Pose
Journal: Hepatology (2023)

Background and Aims: The role of medications for alcohol use disorder (MAUD) in patients with cirrhosis is not well established. Evidence on the efficacy and safety of these drugs in these patients is scarce. Approach and Results: We performed a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol guidelines on the efficacy of MAUD in patients with cirrhosis. A search was conducted in PubMed, Embase, and Scopus, including all studies until May 2022. The population was defined as patients with AUD and cirrhosis. The primary outcome was alcohol abstinence. Safety was a secondary outcome. We performed a random-effect analysis and expressed the results as relative risk of alcohol consumption. Heterogeneity was measured by I 2 . Out of 4095 unique references, 8 studies on 4 different AUD treatments [baclofen (n = 6), metadoxine (n = 1), acamprosate (n = 1), and fecal microbiota transplant (n = 1)] in a total of 794 patients were included. Four were cohort studies, and 4 were RCTs. Only RCTs were included in the meta-analysis. MAUD was associated with a reduced rate of alcohol consumption [relative risk = 0.68 (CI: 0.48–0.97), P = 0.03], increasing alcohol abstinence by 32% compared to placebo or standard treatment, despite high heterogeneity ( I 2 = 67%). Regarding safety, out of 165 serious adverse events in patients treated with MAUD, only 5 (3%) were possibly or probably related to study medications. Conclusion: MAUD in patients with cirrhosis is effective in promoting alcohol abstinence and has a good safety profile. Larger studies on the effects of MAUD are needed, especially in patients with advanced liver disease.